Fig. 4.
(A) Scatter-plot showing IC50 values for MI-2 from multiple glioma cell-lines (x-axis) vs. IC50 for either MI-503 or lanosterol synthase inhibitor (RO-48-8071), with linear regression shown. (B) NMR biochemical assay for enzymatic conversion of 2,3-oxidosqualene to lanosterol by human lanosterol synthase enzyme in the presence of increasing concentrations of MI-nc, MI-2, MI-2–2, MI-503, and RO-48-8071. (Upper) NMR spectra of solutions after reaction at different concentrations of inhibitors. A spectral region contains the NMR peaks originating from lanosterol (28-H at 0.985 ppm and 19-H at 0.963 ppm). Inhibitor concentrations were 0 (black), 0.0017 (blue), 0.005 (light blue), 0.015 (cyan), 0.046 (green), 0.137 (light green), 0.41 (yellow), 1.23 (pale yellow), 3.7 (orange), 11.1 (brown), 33.3 (magenta), and 100 (red) μM. (Lower) FA score vectors representing the dependence on inhibitor concentrations (representative replicate displayed). Those of factors with the five largest eigenvalues are shown (black, red, blue, green, and yellow for first to fifth, respectively).